Palliative pelvic radiotherapy of symptomatic incurable rectal cancer – a systematic review

Figures & data

Figure 1. Study flowchart.

Table I. Characteristics of studies of palliative pelvic radiotherapy of rectal cancer.

Author/year	Study design and treatment period	Participants	Radiotherapy (Dose range/fraction size/treatment period)	Relevant outcome	Follow-up
Allum [18] 1987	Retrospective 1983–1985	N = 18 inoperable recurrent CRC	30–45 Gy/3 Gy 5–10 Gy/single fraction (some repeated)	Pain relief, 3-point scale	NR
Carlsson [14] 1986	Pro, non-randomized, controlled trial, NR	79 inoperable or recurrent rectal cancer RSN = 47 given EBRT	30 or 45 Gy/2 Gy	Pain relief, 4-point scale	1 mo
Ciatto [19] 1982	Retrospective 1956–1976	N = 108 recurrent rectal or RS cancer RSN = 90 symptomatic	35–50 Gy/2 Gy/4–5 wk Boost of 10–15 Gy in a few cases	Complete regression of symptoms	Minimum 5 yr None lost
DeRenzis [20] 1986	Retrospective 1981–1984	N = 35 inoperable or recurrent rectal cancer	Palliation: 40–50 Gy Cure: > 50 Gy	Symptom relief, not defined	35/35–2 yr 21/35–3 yr
Dobrowsky [21] 1985	Retrospective 1975–1982	58 rectal cancer recurrence RSN = 38 symptomatic	15–70 Gy (some given split course)	Pain relief, 4-point scale	Minimum 2 yr None lost
Gescher [22] 1987	Retrospective 1977–1983	N = 61 inoperable recurrent rectal cancer	50 –70 Gy/2–2.5 Gy/5–9 wk	Symptom relief, dichotomized and PI	NR
Guiney [23] 1999	Retrospective 1981–1990	57 residual rectal or RS cancer RSN = 17 palliative treatment, symptomatic	45 Gy/3 Gy/4 wk 30 Gy/5 Gy/4 wk	Symptom relief, 3-point scale	Median 49 mo (range 5–80)
James [24] 1983	Retrospective Period NR	143 symptomatic recurrent rectal cancer RSN = 119 evaluable	< 10 Gy to > 20 Gy	Symptom relief, 3-point scale	NR. 24 lost to follow-up
Kimmig [25] 1989	Retrospective 1979–1985	N = 74 recurrent CRC	60–66 Gy Perineal affection received additional MeV	Pain relief, dichotomized	2–8 yr
Murdock [26] 1964	Retrospective 1957–1962	N = 13 perineal recurrence of CRC RSN = 9 radiotherapy alone	24–56 Gy/2 Gy/1–4 wk	Symptom relief, 4-point scale	NR
Murphy [27] 1964	Retrospective 1942–1961	135 irradiated rectal or RS cancer RSN = 127 inoperable or recurrent	20–60 Gy/2–7 wk	Palliation, not defined	NR
O’Connell [12] 1982	RCT NR	44 inoperable or recurrent rectal or RS cancer RSN = 19 randomized to EBRT alone (control gp)	50 Gy/2 Gy/7 wk (split-course)	Pain relief, not defined	NR
Pacini [28] 1986	Retrospective 1956–1983	N = 143 recurrent rectal or RS cancer	35–65 Gy/2–3 Gy/3–7 wk	Symptom relief, dichotomized and PI	NR. None lost to follow-up
Påhlman [15] 1985	Pro & retrospective 1979–1983	39 inoperable rectal or RS cancer RSN = 27 symptomatic, radiotherapy alone	46 Gy/2 Gy/4–5 wk	Symptom relief, 3-point scale	NR
Ruggieri [29] 1989	Retrospective 1976–1985	N = 68 recurrent rectal cancer	30–60 Gy/1.6–2.5/3–8 wk Some received additional perineal boost	Pain relief, 4-point scale	3 mo
Sinha [30] 1989	Retrospective 1974–1983	48 recurrent rectal or RS cancer RSN = 25 given EBRT alone	Mean 50 Gy/2 Gy/5–5.5 wk 8/25 received additional 2 Gy × 5 boost	Symptom relief, dichotomized	NR
Sklaroff [31] 1973	Retrospective 1961– ?	N = 10 inoperable rectal cancer	40–50 Gy	Symptom relief, not defined	Minimum 6 mo
Smedal [32] 1967	Retrospective NR	N = 50 recurrent rectal or RS cancer (including 2 cases of anal cancer)	20–60 Gy	Palliation, 4-point scale	NR
Soleimani [16] 1972	Retrospective 1955–1969	110 recurrent or metastatic CRC RSN = 79 treatment for pelvic recurrence	400–1750 NSDE	Symptom relief, 4-point scale	NR
Stearns [33] 1970	Retrospective 1965–1968	N = 61 inoperable or recurrent pelvic CRC	20–25 Gy/2–3 wk Several repeated courses	Pain relief, 4-point scale	Through January 1968 or until death
Trotter [13] 1996	RCT 1985–1991	73 inoperable or recurrent rectal cancer RSN = 37 randomized to EBRT alone (control gp)	Median 45 Gy (16.2–54 Gy)/1.5–1.8 Gy/ 5.5 wk (1.5–9)	Reduction in pain score, 4–5-point scale	Until progression or death
Urdaneta-Lafee [34] 1972	Retrospective NR	135 inoperable or recurrent rectal cancer RSN = 102 given EBRT alone	10–60 Gy/2 Gy	Symptom relief, dichotomized	NR. 2 lost to follow-up
Wang [35] 1962	Retrospective 1940–1960	111 inoperable, residual or recurrent rectal, RS or sigmoid cancer RSN = 82 adequate follow-up	< 20 Gy to > 50 Gy	Symptom relief, dichotomized	NR
Williams [36] 1949	Retrospective ?–1946	192 rectal cancer RSN = 128 inoperable (primary and recurrent)	One patient given 50 Gy/4–6 wk	Relief of symptoms, not defined	NR. 2 lost to follow-up
Williams [17] 1956	Retrospective 1937–1954	N = 189 inoperable rectal cancer	Aim 60 Gy/1.5–2 Gy/6–8 wk	Relief of symptoms, 3-point scale	Several yr
Williams [37] 1957	Retrospective NR	N = 82 recurrent rectal cancer	30–60 Gy/3–6 wk	Relief of symptoms, dichotomized	NR
Wise [38] 1959	Retrospective NR	N = 22 recurrent or residual rectal, RS and sigmoid cancer	Mean 46 Gy (30–60) 6 patients previously treated with EBRT	Pain relief, 3-point scale	NR

CRC, colorectal cancer; EBRT, external beam radiotherapy; gp, group; Gy, Gray; MeV, mega electron volt; mo, months; NR, not reported; NSDE, nominal standard dose equivalents; PI, palliative index (symptom-free period relative to survival duration); Pro, prospective; RCT, randomized controlled trial; RS, rectosigmoid; RSN, number of patients in the relevant subgroup; wk, weeks; yr, years.

Figure 2. Arrows indicate no upper or lower limit. • = mean dose only. ♦ = dose reported for only one patient. Study by Soleimani is not listed (dose in NSDE).

Table II. Symptomatic response to palliative pelvic radiotherapy of rectal cancer.

Author	Radiation dose (Gy)	Symptoms included in the reported response*	Response* (positive responses/total)	Duration in months (range)
Allum [19]	5–45	Pain	Pain 13/19	Median 3 (1–7)
Carlsson [14]	30 or 45	Pain	Pain 40/43	Mean 6 (2–10)
Ciatto [20]	35–65	Pain, vaginal bld/dc, rectal do, dysuria	50/90	6: 33%, 12: 15%
DeRenzis [36]	< 40 to > 50	Pain, rectal bld/dc, urinary do, vaginal bld/dc	25/35	6 (or death): 71%
Dobrowsky [21]	15–70	Pain	Pain 34/38	NR
Gescher [22]	50–70	Pain, defecation do, rectal bld/dc, vaginal bld, mass	44/51; Pain 30/33	Mean 9 (0–53), 6: 50%
Guiney [23]	30–45	NS	12/17	NR
James [24]	< 10 to > 20	Pain, mass, bld/dc, urinary, neurologic	83/119	NR
Kimmig [25]	60–66	Pain	Pain 53/74	6–12
Murdock [26]	24–56	Pain, mass/ulceration, dc, edema	5/9	R 5–18, 6: 44%, 12: 33%
Murphy [37]	20–60	Pain, mass	73/127	6: 58%, 12: 42%, 24: 8%
O’Connell [12]	50	Pain	Pain 17/18	Median 5 (1–44+)
Pacini [27]	35–65	Pain, vaginal bld/dc, dysuria, rectal do	115/143	6: 32%, 12: 13%, 24: 6%
Påhlman [15]	46	Bld, pain, altered bowel habit, soiling, incontinence	26/27; Bld 15/15; pain 12/13; altered bowel habit 11/12; soiling 9/10; incontinence 1/3	Median 5 (1–20)
Ruggieri [28]	30–60	Pain, nodules, mass, bld	Pain 45/67	3: 32%
Sinha [29]	Avg 50	Pain, rectal bld/dc, perineal nodules, vaginal dc, diarrhea, dysuria	Pain 13/23; bld 2/3; dc 4/6; diarrhea 2/2; nodules 2/3;dysuria 1/2	NR
Sklaroff [18]	40–50	Bld	10/10; Bld 10/10	6: 90%
Smedal [30]	20–60	Pain, bld/dc, mass	36/50	6: > 50%, 12: > 26%
Soleimani [16]	400–1750 rets^#	“Pelvic syndrome”^¤	“Pelvic syndrome” 57/79	NR
Stearns [35]	20–25	NS	57/61	6: 80%
Trotter [13]	16–54	Pain	Pain 21/37	NR
Urdaneta–Lafee [38]	10–60	Bld, pain, diarrhea, constipation, tenesmus, urinary	85/102	NR
Wang[33]	< 20 to > 50	Pain, mass, bld/dc	69/82; Pain 63/76; mass 12/20; bld/dc 19/20	NR
Williams [34]	NR	Pain, tenesmus, bld, dc, ulceration	60%	NR
Williams [17]	60	Bld, rectal dc, pain, tenesmus	Bld 121/135; dc 77/116; pain 78/102; tenesmus 48/66	NR
Williams [31]	30–60	Pain, mass, dc, bld, urinary, edema, diarrhea	71/82	3: 55%, 6: 32%, 12: 12%
Wise [32]	30–60	Pain, mass, vaginal bld, perineal abscess	Pain 18/18; mass 5/5; vaginal bld 3/3	Mean 4.5 (3 weeks–18 months)

*Symptoms are listed in order of their reported frequencies. *Overall symptomatic response (in bold), unless otherwise stated. ¤, bleeding, tenesmus, discharge, pain, urinary symptoms and edema.

#, nominal standard dose equivalents (NSDE); Bld, bleeding; dc, discharge; do, disorder; NR, not reported; NS, not specified other than as “symptoms”; R, range.

Table III. Pooled symptomatic response rates according to authors’ own definitions, at variable time points after palliative pelvic radiotherapy.

Symptom	Response*
Overall response, including “pelvic syndrome” [15,16,18,20,22–24,26,27,30, 31,33, 35–38] (specific symptom not indicated)^¤	818/1084 = 75%
Pain [12–15,17,19,21,22,25,28,29,32,33]	437/561 = 78%
Bleeding and discharge [15,17,18,29,32,33]	251/308 = 81%
Mass and tenesmus [17,32,33]	65/91 = 71%
Other (diarrhea, nodules, dysuria, etc) [15,29]	26/32 = 72%

*Symptomatic responses are dichotomized as “response” or “no response”.

¤Williams’ 1949 study is not included in the table because the number of responses cannot be determined.

Table IV. Toxicity reported in studies of palliative pelvic radiotherapy of rectal cancer.

Author	Gastrointestinal	Genitourinary	Skin/connective tissue
Allum [19]	mild*	NR	NR
Carlsson [14]	none observed	none observed	none observed
Ciatto [20]	mild, no late	NR	mild
DeRenzis [36]	mild	mild	mild
Dobrowsky [21]	mild	mild	mild
Gescher [22]	enteritis requiring operation 2/51	NR	mild 23/51
Guiney [23]	moderate** 3/27, no late	NR	moderate 1/27
James [24]	mild 13/119, severe*** 8/119	NR	NR
Murdock [26]	NR	NR	mild
O’Connell [12]	mild – moderate SBO 3/19	NR	NR
Pacini [27]	mild	NR	mild
Sinha [29]	mild – moderate 9/25 adhesions 1/25, SBO 1/25	NR	mild 1/25 fibrosis 1/25
Sklaroff [18]	mild	NR	fibrosis 3/10
Smedal [30]	severe 4/50	anuria (pelvic scarring) 1/50	NR
Stearns [35]	mild	NR	NR
Trotter [13]	11/37 grade 3 or 4 (WHO criteria)	NR	NR
Urdaneta-Lafee [37]	mild – moderate	NR	NR
Williams [34]	mild – moderate bowel reactions 24/192, pain 6/192, fistula 12/192, stricture 32/192	moderate 19/192	mild necrosis 6/192
Williams [17]	mild – moderate rectal stenosis 1/189, fistula 12/189	mild – moderate	mild – moderate fibrosis 32/189, necrosis 9/189
Williams [31]	mild – moderate	moderate	severe necrosis 2/82
Wise [32]	mild – moderate 11/22, severe 3/22	moderate 2/22	moderate – severe 5/22

Late complications are indicated in bold type text.

NR, not reported; SBO, small bowel obstruction; WHO, World Health Organization.

*Mild indicates that the author has described the toxicity as “mild” or as not requiring more than symptomatic measures.

**Moderate indicates that the author has described the toxicity as “moderate” or that the treatment was interrupted due to toxicity.

***Severe indicates that the author has described the toxicity as “severe” or that the treatment was discontinued due to toxicity.

Pahlman L, Glimelius B, Ginman C, Graffman S, Adalsteinsson B. Preoperative irradiation of primarily non-resectable adenocarcinoma of the rectum and rectosigmoid. Acta Radiol Oncol 1985;24:35–9.

 PubMed Web of Science ®Google Scholar

Sanderson S, Tatt ID, Higgins JP. Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: A systematic review and annotated bibliography. Int J Epidemiol 2007;36:666–76.

 PubMed Web of Science ®Google Scholar

Soleimani PK, Hindo WA, Hendrickson FR. Dose-response relationship in radiation therapy of advanced carcinoma of the colon and rectum. Radiology 1972;103:179–81.

 PubMed Web of Science ®Google Scholar

Williams IG, Horwitz H. The primary treatment of adenocarcinoma of the rectum by high voltage roentgen rays (1,000 kv). Am J Roentgenol Radium Ther Nucl Med 1956;76:919–28.

 PubMedGoogle Scholar

Sklaroff DM. Radiation as primary therapy for rectal carcinoma. Am Fam Physician 1973;8:81–5.

 PubMed Web of Science ®Google Scholar

Allum WH, Mack P, Priestman TJ, Fielding JW. Radiotherapy for pain relief in locally recurrent colorectal cancer. Ann R Coll Surg Engl 1987;69:220–1.

 PubMed Web of Science ®Google Scholar

Ciatto S, Pacini P. Radiation therapy of recurrences of carcinoma of the rectum and sigmoid after surgery. Acta Radiol Oncol 1982;21:105–9.

 PubMed Web of Science ®Google Scholar

Dobrowsky W, Schmid AP. Radiotherapy of presacral recurrence following radical surgery for rectal carcinoma. Dis Colon Rectum 1985;28:917–9.

 PubMed Web of Science ®Google Scholar

Gescher FM, Keijser AH. [Palliative radiotherapy of recurrence in rectal carcinoma].Ned Tijdschr Genees 1987;131:533–5.

 PubMedGoogle Scholar

Guiney MJ, Smith JG, Worotniuk V, Ngan S. Results of external beam radiotherapy alone for incompletely resected carcinoma of rectosigmoid or rectum: Peter MacCallum Cancer Institute experience 1981–1990. Int J Radiat Oncol Biol Phys 1999;43:531–6.

 Web of Science ®Google Scholar

James RD, Johnson RJ, Eddleston B, Zheng GL, Jones JM. Prognostic factors in locally recurrent rectal carcinoma treated by radiotherapy. Br J Surg 1983;70:469–72.

 PubMed Web of Science ®Google Scholar

Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. J Clin Epidemiol 2009;62:e1–34.

 PubMedGoogle Scholar

Kimmig B, Engenhart R, Flentje M, Marin-Grez M, Hover KH. [Radiotherapy using photons and neutrons in recurrences of colorectal tumors]. Rontgen-Blatter 1989; 42:47–50.

 Google Scholar

O’Connell MJ, Childs DS, Moertel CG, Holbrook MA, Schutt AJ, Rubin J, et al. A prospective controlled evaluation of combined pelvic radiotherapy and methanol extraction residue of BCG (MER) for locally unresectable or recurrent rectal carcinoma. Int J Radiat Oncol Biol Phys 1982; 8:1115–9.

 PubMed Web of Science ®Google Scholar

Murdock MG, Kramer S. Cobalt 60 therapy in the management of perineal recurrence from carcinoma of rectum and colon. Am J Roentgenol Radium Ther Nucl Med 1964;91:149–54.

 PubMedGoogle Scholar

Pacini P, Cionini L, Pirtoli L, Ciatto S, Tucci E, Sebaste L. Symptomatic recurrences of carcinoma of the rectum and sigmoid. The influence of radiotherapy on the quality of life. Dis Colon Rectum 1986;29:865–8.

 PubMed Web of Science ®Google Scholar

Grillo Ruggieri F, Siragusa A. [Radiotherapy of recurrences of adenocarcinoma of the rectum after radical surgery: Galliera Hospitals (1976–1985)].La Radiol Med 1989; 78:363–6.

 PubMedGoogle Scholar

Sinha PP. Radiation therapy with/without simultaneous weekly 5 F.U. in locally recurrent carcinoma of the recto-sigmoid. W V Med J 1989;85:137–41.

 PubMedGoogle Scholar

Trotter JM, Edis AJ, Blackwell JB, Lamb MH, Bayliss EJ, Shepherd JM, et al. Adjuvant VHF therapy in locally recurrent and primary unresectable rectal cancer. Aust Radiol 1996;40:298–305.

 PubMedGoogle Scholar

Smedal MI, Wright KA, Siber FJ. The palliative treatment of recurrent carcinoma of rectum and rectosigmoid with 2 mv. radiation. Some results and description of a technique. Am J Roentgenol Radium Ther Nucl Med 1967;100:904–8.

 PubMedGoogle Scholar

Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.0.2. The Cochrane Collaboration 2009.

 Google Scholar

Williams IG, Shulman IM, Todd IP. The treatment of recurrent carcinoma of the rectum by supervoltage x-ray therapy. Br J Surg 1957;44:506–8.

 PubMed Web of Science ®Google Scholar

Wise RE, Smedal MI. Palliative treatment of recurrent rectosigmoidal neoplasms with two million volt radiation. Surg Clin North Am 1959;39:775–80.

 PubMed Web of Science ®Google Scholar

Wang CC, Schulz MD. The role of radiation therapy in the management of carcinoma of the sigmoid, rectosigmoid, and rectum. Radiology 1962;79:1–5.

 PubMed Web of Science ®Google Scholar

Carlsson G, Hafstrom L, Jonsson PE, Ask A, Kallum B, Lunderquist A. Unresectable and locally recurrent rectal cancer treated with radiotherapy or bilateral internal iliac artery infusion of 5-fluorouracil. Cancer 1986;58:336–40.

 PubMed Web of Science ®Google Scholar

Williams IG. Carcinoma of the rectum and anal canal; treatment with very high voltage x-ray therapy. Br J Surg 1949;36:376–81.

 PubMed Web of Science ®Google Scholar

Stearns MW, Jr., Whiteley HW, Jr., Leaming RH, Deddish MR. Palliative radiation therapy in patients with localized cancer of the colon and rectum. Dis Colon Rectum 1970; 13:112–5.

 PubMed Web of Science ®Google Scholar